Comparing Everolimus and Sirolimus in Renal Transplant Recipients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparing Everolimus and Sirolimus in Renal Transplant Recipients (NCT01976390), a randomized na study. The primary outcome is Number of Participants With Composite Endpoint of Graft Survival (Non-death Censored) and Biopsy Proven Acute Rejection at 1 Year.

2. Clinical Question

This is a question about comparative outcomes under a particular post-transplant regimen, not a comparison of the drugs in every clinical setting. The setting and accompanying regimen matter because the endpoint was intended to assess immunosuppressive protection in the stated protocol. The record gives the study objective, interventions and endpoint definition, but not the outcome counts needed to assess whether the groups differed.

Equivalence is a specific statistical claim: it requires a prespecified range of differences considered acceptably small and an analysis that evaluates whether the data are sufficiently precise to exclude differences outside that range. The registry record does not report an equivalence margin, a confidence interval, or the analysis of the primary endpoint. The stated objective therefore describes the question the pilot was designed to address; it does not establish that equivalence was demonstrated.

3. Trial Design

The registry identifies this as a randomized, parallel-group, open-label study. Its official title calls it a prospective, single-center pilot study. The listed enrollment is 60, and the study status is completed. The registry lists the phase as NA. The start date is 2013-10-01 and the primary completion date is 2018-07-11.

Participants were assigned to everolimus or sirolimus. The everolimus arm used Zortress, with an initial dose of 0.75 mg twice daily on the day of transplant, taken alongside Neoral. The sirolimus arm used Rapamune, dosed at 5 mg/d on the day of transplant and then decreased to 3 mg/d. The official title places the comparison within a regimen involving low-dose Neoral dosed by C2 monitoring, thymoglobulin induction and rapid steroid discontinuation. The registry record does not report further details of dose adjustment, adherence, or treatment changes.

Random allocation is intended to make treatment groups comparable on average, including for factors that were not measured, but it does not guarantee balance in a pilot study. The registry record does not describe the randomization sequence, allocation concealment, stratification, or procedures for implementing assignment. Masking is listed as none, so the study was open-label. The record does not specify whether outcome assessment or pathology review was independently masked.

The parallel design means the intervention groups were compared during the same study rather than through a crossover. The registry record does not report a protocol, a sample-size justification, or the planned analysis details. It identifies the study as a pilot, but does not state what feasibility criteria, if any, defined that role.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Kidney Transplant Patients at Ohio State University Medical Center taking either everolimus or sirolimus.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Composite Endpoint of Graft Survival (Non-death Censored) and Biopsy Proven Acute Rejection at 1 Year, measured over 1 Year.

The primary endpoint is listed as the number of participants with a composite endpoint of graft survival, non-death censored, and biopsy-proven acute rejection at 1 Year. The description says the endpoint was intended to assess immunosuppressive protection after renal transplantation in the study regimen. The registry lists the unit as participants and the outcome parameter as a count of participants.

A composite endpoint combines multiple clinical components into a single outcome definition. In general, a composite can capture more than one aspect of a study question and may produce an outcome that occurs more often than any individual component. Its interpretation depends on the precise rule used to classify participants: which events count, how components are combined, and how events are handled when more than one component occurs. The registry record does not provide further operational detail about that classification.

The endpoint includes graft survival and biopsy-proven acute rejection, which represent distinct aspects of post-transplant outcome. Reporting the composite alone would not necessarily show how each component contributed. The registry record does not report component-specific counts or a comparative analysis. It also does not provide a confidence interval, equivalence margin, or other estimate that would establish the precision of a difference between groups. Accordingly, the endpoint definition clarifies the intended outcome, but the posted registry data do not permit an assessment of the primary comparative question.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Randomization is a method for assigning participants to study groups by chance. In general, this helps prevent treatment assignment from being determined by prognosis or clinical judgment and can support causal comparisons. It does not ensure that every prognostic characteristic is balanced, especially in a pilot study. The registry record labels allocation as randomized but does not describe the sequence-generation method, concealment, implementation, or any stratification. Those details are not reported in the registry record, so the conduct of randomization cannot be evaluated from the entry alone.

What does open-label mean?

Masking describes whether participants, clinicians, outcome assessors, or analysts are kept unaware of assigned treatment. The record lists masking as none. In general, open-label treatment can influence care decisions, adherence, reporting of symptoms, or outcome assessment. Some endpoints are more susceptible to such influence than others. Biopsy-proven acute rejection involves a diagnostic determination, while the record does not say whether biopsy assessment was masked or how the diagnosis was adjudicated. It would be inappropriate to assume that assessment was either masked or unmasked beyond the registry's stated absence of masking.

How should a composite endpoint be understood?

A composite endpoint groups multiple outcomes under a shared classification rule. In general, this can reflect a study question that spans different clinical events and can make an endpoint more informative than a single component when the components are aligned with the objective. Interpretation depends on the definition and on the component results. A combined count may conceal differences in the frequency or importance of its components, so component-level reporting helps readers understand what drove the composite. The registry identifies graft survival, non-death censored, and biopsy-proven acute rejection, but does not report component-specific findings or explain the exact rule for classifying participants with these outcomes.

The endpoint is recorded as a participant count at 1 Year. A count is a descriptive measure of how many participants meet an outcome definition. For a comparison, counts are usually interpreted alongside the group denominators and a suitable estimate of uncertainty. The registry record does not include the primary outcome counts, an effect estimate, or an uncertainty interval, so a comparative estimate cannot be interpreted. No recalculated primary comparison is available from the posted information.

What does equivalence require?

In general, an equivalence study assesses whether a difference is small enough to fall within a prespecified margin on both sides of a target value. The margin must be justified before looking at the results, and the analysis must reflect that objective. A confidence interval communicates the range of effect sizes compatible with the observed data under the model and assumptions. For equivalence, the interval is assessed against the margin rather than relying only on whether a difference test is statistically significant. The registry record does not report an equivalence margin, a confidence interval, or the primary analysis, so it does not permit this assessment.

A confidence interval is a way to express statistical precision, not a guarantee that the true effect lies within a particular interval. Wider intervals generally indicate less precision, while narrower intervals indicate greater precision, conditional on the data and statistical assumptions. The record does not report a primary-effect interval. Consequently, readers cannot assess how much uncertainty remains around the primary comparison or whether the data exclude clinically important differences.

What role does the pilot designation play?

The official title describes the study as a pilot. In general, pilot studies can help assess procedures, recruitment, treatment delivery, or the feasibility of a larger study, but the designation alone does not establish which purpose applied. The registry record does not report feasibility criteria or a sample-size justification. It also does not report a statistical analysis plan. It is therefore not possible to determine from the record whether the enrollment was selected for feasibility, precision, or another reason.

The record includes a general description of planning illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect, and that participant-based planning quantities are expressed per arm except for time-to-event outcomes. These are planning assumptions, not observed trial findings or evidence of achieved power. The record does not report a primary endpoint estimate from which to interpret such planning illustrations, and they cannot substitute for a reported analysis of the trial.

Over-dispersion is a general issue when count outcomes vary more than an assumed statistical model expects. When present, it can make standard errors too small and confidence intervals too narrow if the model does not account for the extra variation. The primary outcome is described as a participant count, but the record does not report a model, dispersion estimate, or inferential analysis. There is no basis to say whether over-dispersion was assessed or relevant to the primary analysis.

Statistical significance and clinical importance are different concepts. A significance test evaluates compatibility of the observed data with a model-based null hypothesis; it does not determine whether an effect is meaningful in practice. Effect estimates and confidence intervals, interpreted alongside a prespecified clinical margin, are important for assessing magnitude and precision. Those details are not reported for the primary endpoint. As a result, neither statistical evidence for a difference nor evidence of equivalence can be inferred from the registry entry.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and reports no analyses. It does not describe a statistical analysis plan, a hierarchy of outcomes, or a method for controlling multiplicity. Multiplicity arises in general when several outcomes, time points, subgroups, or statistical tests are considered; repeated testing can increase the chance of a chance finding. The record does not report whether secondary or exploratory analyses were planned or performed, so no conclusion about multiplicity adjustment is possible.

Missing-data handling is not reported in the registry record. There is no description of participant withdrawals, incomplete outcome ascertainment, missing biopsies, or rules for handling unavailable measurements. The registry entry also does not identify analysis populations such as intention-to-treat or per-protocol populations. These omissions matter because different analysis populations and missing-data assumptions can affect a treatment comparison, particularly when the stated aim is equivalence.

The record does not report participant flow by treatment arm, exclusions after randomization, adherence, crossovers, or treatment discontinuation. It also does not state whether all randomized participants were included in the endpoint analysis. These details are necessary to assess how closely the analysis preserved the randomized comparison and whether missing outcomes could bias interpretation. Without those details or an endpoint analysis, the posted results do not support a complete evaluation of the trial's statistical methods.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: serious adverse effects (89.5%).

The registry lists serious adverse events for the everolimus arm as 35 affected among 41 at risk, and for the sirolimus arm as 17 affected among 19 at risk. It lists no deaths in either group and no affected participants under the other adverse-event count shown. The serious adverse effects term is reported as 89.5%. These are descriptive entries in the registry, not a formal comparison of risk between treatments.

Affected counts and at-risk counts should be read together. In general, an affected count describes participants with a recorded event under the registry's reporting definition; it does not show event timing, severity distribution, recurrence, or the number of individual events. The record does not provide further definitions or follow-up details for these entries. It also does not provide confidence intervals, a hypothesis test, or adjustment for exposure time.

The listed serious-event counts do not establish that one treatment is safer than the other. Differences in group size, event ascertainment, follow-up, and reporting can affect descriptive counts, and the record does not provide the information needed to evaluate those factors. The serious adverse effects term and percentage should be interpreted as registry reporting, not as a separate causal estimate or a complete account of harms.

12. What the Result Does, and Does Not, Mean

The registry record establishes what comparison the investigators intended to make: everolimus versus sirolimus after renal transplantation, within the described immunosuppression regimen. It identifies a randomized, parallel, open-label pilot design and defines a primary composite endpoint at 1 Year. It also provides serious adverse-event counts. This information helps readers understand the study question and the limits of the recorded findings.

The record does not report the primary endpoint results or a comparative efficacy analysis. It therefore does not establish whether graft survival or biopsy-proven acute rejection differed between the treatment groups. It also does not establish that the treatments were equivalent. That conclusion would require a reported analysis with a suitable equivalence margin and enough precision to rule out differences beyond that margin; these items are not reported in the registry record.

The safety counts are not sufficient to determine comparative safety. They do not include uncertainty estimates or the detail needed to account for event timing, follow-up, or ascertainment. The counts can be described as recorded, but they should not be read as proof that either regimen caused more or fewer serious events.

In general, a randomized study can support a treatment comparison when allocation, follow-up, outcome measurement and analysis are adequately conducted and reported. Here, the registry record does not provide enough detail to assess several of those features. The study's completed status and listed enrollment do not fill in missing outcome results. Nor does the pilot label say, by itself, how the study should be interpreted or what degree of precision it achieved.

The appropriate conclusion is narrow: the record documents the design, interventions, intended endpoint, and selected safety data, but does not provide the primary outcome analysis needed to answer the central comparative question. No claim that either treatment is superior, equivalent, or inferior follows from the registry information alone.

13. Why This Trial Matters Statistically

This trial is statistically interesting because its stated objective is equivalence, while the registry entry does not report the ingredients needed to evaluate an equivalence claim. Equivalence is not the same as failing to find a statistically significant difference. It depends on a prespecified margin and an estimate precise enough to place the plausible treatment difference inside that margin. The absent margin and primary analysis leave the central inferential question unresolved.

The study also illustrates why endpoint definitions matter. Its primary outcome combines graft survival, non-death censored, with biopsy-proven acute rejection. A composite can represent more than one aspect of a clinical question, but interpretation depends on the exact classification rule and component-level findings. Those details are not reported in the registry entry. A single composite count, even if reported, would need context about its components and uncertainty.

Randomization provides a sound basis for comparing groups in principle, but reliable interpretation also depends on transparent reporting of assignment, follow-up, missing outcomes, analysis populations, and statistical methods. The record supplies only limited design information and no primary endpoint analysis. This makes the trial a useful example of the distinction between a stated objective and evidence that can be independently interpreted from a registry record.

The adverse-event counts further illustrate the difference between descriptive data and comparative inference. Counts identify reported events, but without uncertainty estimates and details of follow-up and ascertainment they do not establish relative risk. In general, statistical interpretation requires both the observed data and a clear account of how those data were analyzed. The record's omissions are therefore substantive limits on what can be concluded, not merely missing technical detail.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record does not report results for the primary composite endpoint, its components, or a between-arm estimate. This is the central limitation for interpreting the study's efficacy question. It also does not report a confidence interval, a statistical test, or the equivalence margin needed to assess the stated equivalence objective.

The record provides limited information about trial conduct. Although allocation is listed as randomized and masking as none, it does not describe sequence generation, concealment, treatment implementation, outcome adjudication, or whether biopsy assessment was masked. It does not report baseline characteristics, participant flow by arm, adherence, treatment changes, withdrawals, or analysis populations. Missing-data methods and the handling of incomplete outcome ascertainment are not reported in the registry record.

The safety information is also limited. The registry lists affected and at-risk counts, but does not report event definitions, timing, duration of follow-up, recurrent events, exposure time, uncertainty estimates, or a comparative analysis. The entries therefore cannot support a full assessment of relative safety.

The record describes the trial as a pilot but does not report the rationale for enrollment, a sample-size justification, feasibility criteria, or the planned statistical analysis. The planning description does not replace these details or provide an observed primary result. The record identifies a single-center setting and a specific immunosuppression regimen, so findings, if reported elsewhere, would need to be interpreted in that context. No further population or generalizability details are reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Comparing Everolimus and Sirolimus in Renal Transplant Recipients — NCT01976390.
• Registry record last updated 2022-10-21; status last verified 2021-11.
• Results first posted 2021-11-30.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT01976390 is a completed, randomized, parallel, open-label, single-center pilot study sponsored by Ohio State University. The listed enrollment is 60. The record compares Zortress (everolimus) with Rapamune (sirolimus) in renal transplant recipients under a regimen described as including Neoral, thymoglobulin induction and rapid steroid discontinuation. The registry lists the phase as NA.

The primary endpoint is the number of participants with a composite of graft survival, non-death censored, and biopsy-proven acute rejection at 1 Year. The registry record does not report an analysis or results for that endpoint, nor an equivalence margin. Serious adverse-event counts are listed as 35 affected among 41 at risk for everolimus and 17 among 19 for sirolimus; no deaths are listed in either group. These safety entries are descriptive and do not provide a comparative analysis.